Hospital Drug Research Articles

The Association Between Medication Use in Older Women with Early-Stage Operable Primary Breast Cancer and Decision Regarding Primary Treatment.

Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status. A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of diagnosis of breast cancer. Association was determined between number of medications and treatment decision and physical status as measured by the CGA outcomes. Additional analysis was performed to determine the associations above with polypharmacy defined by ≥5 daily medications, and if cardiovascular-related diseases have a role in the treatment decision. Polypharmacy was present in 48% of patients (n = 139). CGA determined that polypharmacy was associated with greater comorbidity (P < .001), reduced physical status rated by physicians (P = .009) and patients (P = .019), and reduced ability to perform activities of instrumental ADLs (P = .008). Similar findings were present in the analysis of cardiovascular-related diseases. This work suggests that patients with polypharmacy are more likely to be frail. The number of medications could help us screen patients who should go on to receive full CGA.

Study on the accessibility and affordability of 50 drugs in Wuhan based on the WHO/HAI standardization method.

To understand the availability and affordability of essential drugs in Wuhan since the implementation of the national essential medicine system, and to provide a basis for the subsequent formulation and improvement of related policies. Using the standard survey method jointly developed by the WHO and Health Action International (HAI), a sample of 50 essential drugs was selected to investigate and evaluate their availability and affordability in public medical and health institutions and social retail pharmacies in Wuhan, using six diseases with high clinical morbidity as the targets. The availability of the original drug and the lowest-priced generic drug in public hospitals is 26.4 and 42.47% respectively, and that in retail pharmacies is 26.8 and 54.4% respectively. The median price ratio of the original drug and the lowest-priced generic drug is 28.71 and 2.23 respectively in public hospitals, and 29.24 and 3.59 respectively in retail pharmacies; In addition to individual drugs, such as omeprazole, others are affordable. The availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs. The availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs. The price of the original drug is much higher than the international reference price; The price of medicines in public hospitals is lower than that in retail pharmacies;the overall condition of affordability is good, but there is a big gap between the affordability levels of original drugs and generic drugs, and the affordability of original drugs is relatively poor. It is recommended to adjust the relevant policies according to the actual situation of Wuhan city itself, moderately ensure the supply of original drugs, improve the price transparency of retail pharmacies, and ensure that the basic drug needs of the public are met.

Comparing substance use treatment initiation and retention between telehealth delivered during COVID-19 and in-person treatment pre-COVID-19.

A large portion of veterans referred to substance use disorder (SUD) treatment do not attend their first appointment or leave treatment prematurely. Telehealth options may increase access to care and treatment attendance. This study compared treatment initiation and retention between in-person treatment pre-COVID-19 and telehealth treatment during COVID-19 in a VA hospital outpatient alcohol and drug treatment clinic. Electronic health record data were collected on 373 veterans out of 481 referrals. Mixed logistic and negative binomial regression models were used for estimating the effect of treatment modality on treatment initiation and retention, respectively. The odds of initiating treatment were 2.6 times greater when referred to a telehealth appointment during COVID-19 compared to an in-person appointment pre-COVID-19. Months retained in treatment postinitiation was similar between treatment modalities. Each month in treatment corresponded to a subsequently lower rate of treatment session attendance and by the fourth month, the average number of sessions attended was significantly lower for those receiving in-person treatment compared to those receiving telehealth treatment. The odds of initiating SUD treatment and rate of treatment attendance over time was greater for services delivered via telehealth during COVID-19 compared to in-person pre-COVID-19. Extending telehealth services as an option for individual and group SUD treatment may promote treatment initiation and potentially higher rate of attendance over time. This study provides additional evidence for the feasibility and utility of rapidly expanding telehealth for veterans seeking outpatient substance use treatment.

Analysis of Prescribing Patterns and Adverse Drugs Reactions in Diabetic Patients at Tertiary Care Hospital, Lucknow

To study the prescribing pattern and adverse drug reactions (ADRs) of anti-diabetic drugs in a tertiary care hospital in Lucknow, India. Methods: A prospective study was conducted over a period of 6 months at the inpatient and outpatient departments of the hospital. A total of 100 patients with diabetes were included in our study. Demographic characteristics were recorded and 100 prescriptions were analyzed. ADRs were reported and analyzed. Results: Among the 100 patients, 58 were male and 42 were female. The majority of the patients were in the age group of 41-60 years. Biguanides (38%) and sulphonylureas (31%) were the most commonly prescribed anti-diabetic drugs. A total of 8 ADRs were reported, including hypoglycemia, gastric irritation, and abdominal discomfort. Metformin had the highest number of ADRs among the oral hypoglycemic drugs. Conclusion: The study showed that the prescribing pattern of anti-diabetic drugs in the hospital was in line with the essential medicine list. ADRs were reported, with hypoglycemia being the most common ADR observed. Continuous monitoring and reporting of ADRs is necessary for the safe and effective use of anti-diabetic drugs.

Analysis of Prescribing Patterns and Adverse Drugs Reactions in Diabetic Patients at Tertiary Care Hospital, Lucknow

To study the prescribing pattern and adverse drug reactions (ADRs) of anti-diabetic drugs in a tertiary care hospital in Lucknow, India. Methods: A prospective study was conducted over a period of 6 months at the inpatient and outpatient departments of the hospital. A total of 100 patients with diabetes were included in our study. Demographic characteristics were recorded and 100 prescriptions were analyzed. ADRs were reported and analyzed. Results: Among the 100 patients, 58 were male and 42 were female. The majority of the patients were in the age group of 41-60 years. Biguanides (38%) and sulphonylureas (31%) were the most commonly prescribed anti-diabetic drugs. A total of 8 ADRs were reported, including hypoglycemia, gastric irritation, and abdominal discomfort. Metformin had the highest number of ADRs among the oral hypoglycemic drugs. Conclusion: The study showed that the prescribing pattern of anti-diabetic drugs in the hospital was in line with the essential medicine list. ADRs were reported, with hypoglycemia being the most common ADR observed. Continuous monitoring and reporting of ADRs is necessary for the safe and effective use of anti-diabetic drugs.

Analysis of Prescribing Patterns and Adverse Drugs Reactions in Diabetic Patients at Tertiary Care Hospital, Lucknow

To study the prescribing pattern and adverse drug reactions (ADRs) of anti-diabetic drugs in a tertiary care hospital in Lucknow, India. Methods: A prospective study was conducted over a period of 6 months at the inpatient and outpatient departments of the hospital. A total of 100 patients with diabetes were included in our study. Demographic characteristics were recorded and 100 prescriptions were analyzed. ADRs were reported and analyzed. Results: Among the 100 patients, 58 were male and 42 were female. The majority of the patients were in the age group of 41-60 years. Biguanides (38%) and sulphonylureas (31%) were the most commonly prescribed anti-diabetic drugs. A total of 8 ADRs were reported, including hypoglycemia, gastric irritation, and abdominal discomfort. Metformin had the highest number of ADRs among the oral hypoglycemic drugs. Conclusion: The study showed that the prescribing pattern of anti-diabetic drugs in the hospital was in line with the essential medicine list. ADRs were reported, with hypoglycemia being the most common ADR observed. Continuous monitoring and reporting of ADRs is necessary for the safe and effective use of anti-diabetic drugs.

Ceftriaxone Use Evaluation in Western Zone Tigray Hospitals, Ethiopia: A Retrospective Cross-Sectional Study.

Drug use evaluation is a systematic approach to determining the appropriateness of drug use, identifying drug therapy problems, and proposing interventions. Ceftriaxone is one of the most widely used drugs in hospitals, requiring the performance of drug use evaluation. This study was aimed at evaluating the appropriateness of ceftriaxone use at Kahsay Abera and Mearg hospitals in the Western zone of Tigray, Ethiopia. An institution-based retrospective cross-sectional study design was conducted in both hospitals from December 2015 to August 2016 using standardized and pretested data collection formats. Systematic random sampling was used, and a total of 800 patients' medication records (patients who took ceftriaxone) from both hospitals (400 each) were assessed in this study. Statistical analysis was performed by using the statistical package for social sciences (version 20). The overall appropriateness of ceftriaxone use in Kahsay Abera and Mearg hospitals was 247 (61.75%) and 252 (63.0%), respectively. The majority of inappropriate use of ceftriaxone was noted in indication errors at both Kahsay Abera (71.2%) and Mearg hospitals (52.0%). The treatment duration in Kahsay Abera (69%) and Mearg hospitals (88%) was in the range of 2-7 days. Mostly, a 2-gram ceftriaxone daily dose was prescribed in both Kahsay Abera and Mearg hospitals, accounting for 285 (71.25%) and 318 (79.5%), respectively. In this study, the top three diseases, indicated for ceftriaxone in both hospitals, were typhoid fever, urinary tract infection, and pneumonia in descending order. Among the medications coadministered with ceftriaxone, the top three coprescribed drugs with ceftriaxone in Kahsay Abera Hospital were metronidazole (17.25%), tramadol 68 (11.28%), and diclofenac (8.96%), but in Mearg Hospital, next to metronidazole, drugs like paracetamol and doxycycline were the most common coprescribed medicines along with ceftriaxone. The appropriateness of ceftriaxone use in Kahsay Abera and Mearg hospitals was 247 (61.8%) and 252 (63%), respectively, in which about one-third of patients' charts were not compliant with the standard treatment guidelines of Ethiopia for general hospitals. In Kahsay Abera and Mearg hospitals, the empiric use of ceftriaxone was 262 (65.5%) and 375 (93.8%), respectively.

Emphasise the effect of Covid-19 patients on antihypertensive drugs in a tertiary care hospital – a cross sectional study

Emphasise the effect of Covid-19 patients on antihypertensive drugs in a tertiary care hospital – a cross sectional study

Audit of Safety Profile of Drugs Being Used to Treat Elderly Type II Diabetics: Observations from a Tertiary Care Hospital

ABSTRACT Background and Objective: The treatment of elderly people who have developed Type II diabetes is a major challenge. Therefore, this study was conducted to ascertain the drug prescription pattern and the adverse effects of drugs in a tertiary care hospital. Methodology: This was a cross-sectional, observational study. This study was carried out on 164 elderly patients with diabetes mellitus attending inpatient and outpatient of the institute. This study assesses the prescribing pattern of antidiabetic drugs and adverse drugs reaction to the drugs administered. Naranjo-Algorithm Probability of American depositary receipt (ADR) scale and WHO prescribing indicators were used for assessment. This study also identifies the drug utilization in diabetic patients associated with other co-morbidities. Results: Mean age of the patient was 72.5 in both inpatient and outpatient and male:female ratio among inpatient and outpatient 1.5:1 and 1:1.3, respectively. Metformin (biguanide) was the most commonly prescribed antidiabetic drug and was followed by glimepiride. Insulin was used in 65% of inpatient. Potential drug-drug interactions were noted in 71% of inpatient and 50.8% of outpatient. The incidence of ADR observed in this study was3.6%. Conclusion: Metformin and glimepiride were the most common drugs used in both inpatient and outpatient groups. Human regular insulin analog was commonly used in both patients group. The poor reporting in pharmacovigilance although mandated by the Indian Council of Medical Research is falling short; in preempting ADR. Effective pharmacovigilance will improve the quality of life in geriatric patients and would help the treating physicians to steer towards safe and effective healthcare.

Analysis of pattern of anti-osteoarthritic drugs in a tertiary care hospital of central India – A drug utilization study

Background: Osteoarthritis (OA) is the most common kind of arthritis and symptomatic OA is recognized as a significant cause of disability and participation limitation in middle-aged and older persons. Aims and Objectives: The present study was done to evaluate drug utilization pattern of drugs used in treatment of OA at tertiary care center in central India. Materials and Methods: The present study was observational and prospective research carried out at NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, a tertiary care hospital. The necessary information was collected from the orthopedics department. The investigation lasted 6 months, from July 2022 to December 2022. The present research included 108 patients diagnosed with OA. Results: The research included a total of 104 patients comprising of 58 females and 44 men. The majority of the patients were found to be 60 years old or older, with OA impacting their knee joint considerably (45%). NSAIDs were the most regularly given class of medicines in OA which was prescribed to 81% of the patients. Combined treatment of NSAIDs, calcium, and Vitamin D3. It was found that 52% of patients were adhering to OA medication. Conclusion: The patient’s uncontrolled pain was brought on by medicines, a low-calcium diet, increased stress, obesity, and advanced age, as well as a lack of knowledge about the challenges associated with OA.

The Impact of the PESTEL Framework in the Green Supply Chain: An Analytical Research in the State Company for Textile and Leather Industries

For each of the steps, we present and justify the models we have chosen. Then, we apply these models in a public hospital "Habib Bourguiba" to manage the supply chain of drugs. Background: In this paper, our objective is to build a performance evaluation system to drive the supply chain of drugs in a public hospital in Tunisia. For this, we consist in making a bibliographical synthesis on performance and the tools for evaluating it and offer an overview of all the methods and models proposed in the literature in order to adopt good practices. evaluation of the performance of supply chains. Objective: From the perspective of developing performance appraisal system, it is imperative to have a robust methodology. In this article, we propose a methodology characterized by a nine-step approach that serves as a guide when designing a system of performance indicators to manage the drug supply chain within Habib Hospital. Bourguiba. Methods: In this paper, we applied the ECOGRAI method. For this, we have identified for each decision center one or more objectives as well as the decision variables associated with them. Then, we determined the performance indicators for each decision center that are consistent with the objectives and the decision variables by referring to this method.

Gambaran Umum Penggunaan Lean Six Sigma Pada Manajemen Obat di RS

The hospital pharmacy installation is an important unit in the hospital that is responsible for pharmaceutical activities. Pharmacy is the last unit and one of the important parts that determine patient satisfaction, to improve the service process in operations management, the method that can be used is lean six sigma to help improve service quality and patient satisfaction by minimizing errors and waiting times through organizing and managing the hospital management system. The purpose of this study is to identify an overview of the use of lean six sigma in drug management in hospitals. This research method is a literature review study with the search engine used in literature searches, namely google scholar according to the keywords of the topic to be studied, namely lean six sigma methods, hospital drug management, lean six sigma implementation, the criteria for articles used are based on publications published between 2019 and 2023. The results showed that there is waste in drug/pharmacy management in hospitals. The problems related to pharmacy include too long waiting times, overprocessing of drug prescriptions, and waste of motion in file searches. SIMRS error, lack of trained human resources, uncertainty of drug prices, still done manually are triggers for the occurrence of worthless processes. Waste reduction can be done with the lean six sigma method which can fix problems that often occur in pharmaceutical installations by being applied through standardized calculations.

When Reality Does Not Meet Expectations-Experiences and Perceived Attitudes of Dutch Stakeholders Regarding Payment and Reimbursement Models for High-Priced Hospital Drugs.

This study aimed to identify the current experiences with and future preferences for payment and reimbursement models for high-priced hospital therapies in the Netherlands, where the main barriers lie and assess how policy structures facilitate these models. A questionnaire was sent out to Dutch stakeholders (in)directly involved in payment and reimbursement agreements. The survey contained statements assessed with Likert scales, rankings and open questions. The results were analyzed using descriptive statistics. Thirty-nine stakeholders (out of 100) (in)directly involved with reimbursement decision-making completed the survey. Our inquiry showed that currently financial-based reimbursement models are applied most, especially discounts were perceived best due to their simplicity. For the future, outcome-based reimbursement models were preferred, particularly pay-for-outcome models. The main stated challenge for implementation was generating evidence in practice. According to the respondents, upfront payments are currently implemented most often, whereas delayed payment models are preferred to be applied more frequently in the future. Particularly payment-at-outcome-achieved models are preferred; however, they were stated as administratively challenging to arrange. The respondents were moderately satisfied with the payment and reimbursement system in the Netherlands, arguing that the transparency of the final agreements and mutual trust could be improved. These insights can provide stakeholders with future direction when negotiating and implementing innovative reimbursement and payment models. Attention should be paid to the main barriers that are currently perceived as hindering a more frequent implementation of the preferred models and how national policy structures can facilitate a successful implementation.

Manipulated Oral and Rectal Drugs in a Paediatric Swedish University Hospital, a Registry-Based Study Comparing Two Study-Years, Ten Years Apart.

This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All patients aged 1 month−18 years with oral or rectal administrations were included. In total, 140,791 oral and rectal administrations were included in 2009, and 167,945 oral and rectal administrations were included in 2019. The frequency of patients receiving at least one manipulated oral medicine decreased between the study years, both in inpatient units and in the emergency department (from 19% to 17%, p = 0.0029 and from 11% to 5%, p < 0.0001, respectively). The frequency of patients receiving a manipulated rectal medicine also decreased between the study years, both in inpatient units and in the emergency department (from 22% to 10%, p < 0.0001 and from 35% to 7% 2019, p < 0.0001, respectively). The results show a decrease in the manipulation of both oral and rectal medicines to paediatric patients in 2019 compared to 2009. Even though this implies a safer practice, there is still a pronounced lack of child-friendly dosage forms and suitable strengths enabling the safe administration of medicines to sick children.

Macro environment determinants affecting the availability of artemisinin-based combination therapies in Uganda

PurposeArtemisinin-based combination therapies (ACTs) have been developed to treat uncomplicated malaria. However, scanty studies exist to inform the role of macro factors in explaining the nonavailability of ACT in developing countries. Therefore, this paper aims to evaluate the different macro-environment factors affecting the availability of ACTs in the public hospital setting.Design/methodology/approachThis study applied a quantitative methodological approach and structural equation modeling (SEM) to test hypotheses statistically. SEM examines linear causal relationships among variables while accounting for measurement error. Confirmatory factor analysis (CFA) was used to assess model reliability. CFA and SEM were used to determine the shared variance-covariance of variables, define the latent construct and provide a more precise way to account for the error variances associated with the variables, which, if untested, could lead to biased parameter estimates. This was guided by the data collected from 40 general public hospitals with 283 respondents.FindingsThis study’s results support a model for promoting social-cultural, technological and legal factors. The availability of ACTs is significantly affected by legal factors. Improving legal aspects by a unit can enhance ACT availability by 0.59. Political factors scored the least, and they do not influence the availability of malaria drugs.Research limitations/implicationsThe design was quantitative and cross-sectional. Future research could be longitudinal with a mixed-method approach and consider other external stakeholders.Practical implicationsReducing the impact of the nonavailability of antimalarial drugs in general public hospitals requires a holistic concerted and coordinated supply chain approach that tackles the political, economic, social-cultural norms, technological and legal factors.Originality/valueThe authors develop and test a model using macro factors: political, economic, social, cultural, technological and legal factors. This model is relevant for many developing countries to supply chain coordination perpetually experiencing medicine shortages.

Association Between Alcohol Use Disorders and Dementia in 262,703 Dementia-free Finnish Adults: Is Cardiovascular Disease a Mediator?

The possible mediating role of cardiovascular disease (CVD) in the relationship between alcohol use disorders (AUD) and the risk of early-onset (<age 65)and late-onset (≥age 65)dementia lacks formal investigation. Using linked Finnish national register data, a population-based cohort study of 262,703 dementia-free Finnish men and women aged 40 + at baseline (December 31, 1999)was established. AUD and CVD in 1988-2014, and incident dementia in 2000-2014 were identified from Finnish Hospital Discharge Register and/or Drug Reimbursement Register. Causal association and mediation were assessed using mediational g-formula. AUD was associated with a substantial increase in the risk of early-onset dementia in both men (hazard ratio: 5.67, 95% confidence interval: 4.37-7.46) and women (6.13, 4.20-8.94) after adjustments for confounding; but the elevated risk for late-onset dementia was smaller (men: 2.01, 1.80-2.25; women: 2.03, 1.71-2.40). Mediational g-formula results showed that these associations were causal in men with no mediation by CVD as the virtually identical total effect of AUD (early-onset: 5.26, 3.48-7.48; late-onset: 2.01, 1.41-2.87) and direct effect of AUD (early-onset: 5.24, 3.38-7.64; late-onset: 2.19, 1.61-2.96) were found with no indirect effect via CVD. In women, the results were similar for late-onset dementia (total effect: 2.80, 1.70-4.31; direct effect: 2.92, 1.86-4.62) but underpowered for early-onset dementia. AUD increased dementia risk, particularly the risk of early-onset dementia. This elevated risk of dementia associated with AUD was not mediated by CVD. Clinicians should consider the increased risk of dementia in the management of middle-aged and older adults with a history and/or current AUD.

360 CARDIOMEMS HF SYSTEM: CONTINUOUS REMOTE MONITORING FOR OPTIMIZE HF PATIENTS' MANAGEMENT AND RESOURCES CONSUMPTION

Abstract Background Heart failure (HF) alternates phases of stability and phases of exacerbation, with a progressive decline in the patient's functional capacity and quality of life; the need to anticipate and improve the effectiveness of management of HF exacerbation has led to the development of several remote monitoring tools. We report our experience with CardioMEMS HF system (implantable device to monitor changes in pulmonary artery diastolic pressure (PAPd) as early indicator of the onset of worsening HF) in order to optimize the pharmaceutical treatments strategy (e.g. Levosimendan infusion) and to assess the impact on hospital resources consumption and costs. Methods We enrolled 7 patients (69.00±4.88 years; 30% female) with end-stage HF, implanted with CardioMEMS and daily monitored remotely, in order to optimize both tailored adjustment of home therapy and infusions of Levosimendan. More in detail, if the cardiologist detected a tendency for PAPd to rise, patients were contacted for home therapeutic changes. If no further changes were possible, the patient was hospitalized for the infusion of Levosimendan. In order to calculate the impact of this remote monitoring strategy on resources consumption, we collected data on hospitalizations (e.g. causes, numbers, length, high-cost drugs and costs) taking into account the same number of months pre and post-CardioMEMS implant for each patient. Results Following the implantation of CardioMEMS we observed a 45% reduction in the total number of hospitalizations and a 62% reduction in the days of hospitalization (from a total of 421 days before implantation to a total of 159 days post implantation in the observation period). From an economic point of view, a significant hospital cost reduction was recorded in terms of both hospitalization costs (HF related re-hospitalization and CardioMEMS's implant related cost) and drugs infusion costs (hospital stay and drug costs); more specifically, the total savings for the 7 patients are around € 236,000 and total days of hospitalization avoided are around 500 days including the hospitalizations avoided for drugs infusion. Accordingly, was recorded an improvement in patients’ quality of life measured with EQ5D (pre-implantation 75.17±2.06 vs post-implantation 108.60±8.70, p 0.0078). Conclusions Our preliminary results support the usefulness of this system in the remote management of the HF patients and in the re-hospitalization reduction both for exacerbation and drug management. In fact, the parameters’ monitoring through the CardioMEMS device allows a personalized management of drug therapy; more precisely, considering the drug Levosimendan, instead of a periodic standard timing for infusion, a patient-tailored timing of infusion was applied. In conclusion, our innovative strategy contributes to achieve the organizational efficiency of the healthcare facilities, as well as to the adequate use and allocation of financial and human resources with a better outcome for HF patients.

Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells

Morphine, a commonly used antinociceptive drug in hospitals, is known to cross the blood-brain barrier (BBB) by first passing through brain endothelial cells. Despite its pain-relieving effect, morphine also has detrimental effects, such as the potential induction of redox imbalance in the brain. However, there is still insufficient evidence of these effects on the brain, particularly on the brain endothelial cells and the extracellular vesicles that they naturally release. Indeed, extracellular vesicles (EVs) are nanosized bioparticles produced by almost all cell types and are currently thought to reflect the physiological state of their parent cells. These vesicles have emerged as a promising source of biomarkers by indicating the functional or dysfunctional state of their parent cells and, thus, allowing a better understanding of the biological processes involved in an adverse state. However, there is very little information on the morphine effect on human brain microvascular endothelial cells (HBMECs), and even less on their released EVs. Therefore, the current study aimed at unraveling the detrimental mechanisms of morphine exposure (at 1, 10, 25, 50 and 100 µM) for 24 h on human brain microvascular endothelial cells as well as on their associated EVs. Isolation of EVs was carried out using an affinity-based method. Several orthogonal techniques (NTA, western blotting and proteomics analysis) were used to validate the EVs enrichment, quality and concentration. Data-independent mass spectrometry (DIA-MS)-based proteomics was applied in order to analyze the proteome modulations induced by morphine on HBMECs and EVs. We were able to quantify almost 5500 proteins in HBMECs and 1500 proteins in EVs, of which 256 and 148, respectively, were found to be differentially expressed in at least one condition. Pathway enrichment analysis revealed that the "cell adhesion and extracellular matrix remodeling" process and the "HIF1 pathway", a pathway related to oxidative stress responses, were significantly modulated upon morphine exposure in HBMECs and EVs. Altogether, the combination of proteomics and bioinformatics findings highlighted shared pathways between HBMECs exposed to morphine and their released EVs. These results put forward molecular signatures of morphine-induced toxicity in HBMECs that were also carried by EVs. Therefore, EVs could potentially be regarded as a useful tool to investigate brain endothelial cells dysfunction, and to a different extent, the BBB dysfunction in patient circulation using these "signature pathways".

Potential overtreatment in end-of-life care in adults 65 years or older dying from cancer: applying quality indicators on nationwide registries

Background Quality indicators are frequently used to measure the quality of care at the end of life. Whether quality indicators of potential overtreatment (i.e., when the risks outweigh the benefits) at the end of life can be reliably applied to routinely collected data remains uncertain. This study aimed to identify quality indicators of overtreatment at the end of life in the published literature and to investigate their tentative prevalence among older adults dying with solid cancer. Materials and methods Retrospective cohort study of decedents including all older adults (≥65 years) who died with solid cancer between 1 January 2013 and 31 December 2015 (n = 54,177) in Sweden. Individual data from the National Cause of Death Register were linked with data from the Total Population Register, the National Patient Register, and the Swedish Prescribed Drug Register. Quality indicators were applied for the last one and three months of life. Results From a total of 145 quality indicators of overtreatment identified in the literature, 82 (57%) were potentially operationalisable with routine administrative and healthcare data in Sweden. Unidentifiable procedures and hospital drug treatments were the reason for non-operationalisability in 52% of the excluded indicators. Among the 82 operationalisable indicators, 67 measured overlapping concepts. Based on the remaining 15 unique indicators, we tentatively estimated that overall, about one-third of decedents received at least one treatment or procedure indicative of ‘potential overtreatment’ during their last month of life. Conclusion Almost half of the published overtreatment indicators could not be measured in routine administrative and healthcare data in Sweden due to a lack of means to capture the care procedure. Our tentative estimates suggest that potential overtreatment might affect one-third of cancer decedents near death. However, quality indicators of potential overtreatment for specific use in routinely collected data should be developed and validated.

HPR154 Appropriate Use of Anti-PD(L)1 in Paris Public Hospitals (AP-HP): Are the Prescriptions in Compliance with Reimbursed Indications?

In France, hospital drugs are reimbursed only for indications of the marketing authorization approved by the French National Authority for Health (HAS). Drugs are financed by the Diagnosis-Related-Groups (DRG)-based payment system or in addition to the DRGs for innovative and costly medicines. Some off-label indications are also reimbursed, particularly if they are scientifically justified. Use of Anti-PD(L)1 drugs is closely monitored by Authorities because of the high cost of treatments (up to €90K annually per patient) and the growing number of indications. The objectives of this study are to confirm the prescriptions’ compliance with reimbursed indications in Paris University Hospitals (AP-HP, the largest hospital center in Europe, 7 million patients annually), and to evaluate the impact on spending.